tbuckley/cabot-search huggingface dataset:
Home controls of a sample of 2,414 oxygen concentrators. Sous-Commission Technique ANTADIR
Authors: A Sautegeau, B Dautzenberg, J Moulieras, B Billard, D Preville, Guadeloupe Bordelais, D Bourriez, L Duperrier, J Fouin, J Girault, D Grassard, F Kochan, D Lagarde, B Mallebrera, M Masson, J Milane, J Pelote, Y Rambaud, C Lyon, Rennes Rupin, J Stain, P Taine
Journal: European Respiratory Journal (1991)

In France, 12,000 patients receive long-term oxygen therapy at home supplied by oxygen concentrators (OCs) which are provided by a non-profit organization, the National Home Treatment for Respiratory Insufficiency Association (ANTADIR--31 regional associations). OCs are regularly checked at home by technicians from the associations. Technical data, oxygen fraction (Fo2) supplied at working flow-rate and working duration, were recorded by technicians only during the planned home controls. Data were collected from January 15th to February 15th, 1988. Twenty three associations taking care of more than 10,000 OCs participated in the study. 2,414 machines of six different brands were controlled in the study. 77.5% of OCs had a working duration of less than 15,000 h (about 3 yrs). Working flow-rate of OCs was equal to or lower than 2 l.min-1 in 79.2% of cases. Mean Fo2 of the 2,414 measurements was equal to 92 +/- 6%. Three quarters of OCs had an Fo2 equal to or higher than the Fo2 predicted by the manufacturers. Less than 0.3% of machines were out of order (Fo2 less than or equal to 50%). We observed a significant progressive decrease in measured Fo2 in relation to flow-rate and working duration (analysis of variance (ANOVA) 2: p less than 0.001): the higher the flow-rate and the longer the working duration, the lower the Fo2. We conclude that supply of used OCs has to be avoided when the prescribed flow-rate is high, and that systematic technical checks are essential to keep OCs in good working order.
Highlights of This Issue
Journal: Clinical Cancer Research (2016)

Evens, et al, investigated the use of abexinostat, an oral pan-histone deacetylase inhibitor in patients with relapsed/refractory lymphoma.Abexinostat was particularly efficacious in follicular lymphoma with a 64% response rate in evaluable patients.Furthermore, responses were durable with median duration of response not reached and median progression-free survival of 20.5 months.Using unique intermittent dosing, abexinostat was well tolerated with thrombocytopenia, fatigue, and neutropenia as the only grade 3/4 adverse events occurring in 10% of patients.Altogether, abexinostat represents a potential new treatment for lymphoma and further investigation is warranted.
A Winter Survey of Domestic Heating among Elderly Patients
Authors: R Morgan, A Blair, D King
Journal: Journal of the Royal Society of Medicine (1996)

Elderly people have a greater need for domestic heating given the time they spend at home and the decline in the body thermoregulation that occurs with ageing. The use of domestic heating by 200 mentally competent newly admitted elderly in patients was evaluated by means of a questionnaire survey. Most patients (69%) were aware of the addition of value added tax (VAT) to their fuel bill and 31% said they had reduced the amount of heating they use because of this. A third of patients (29.5%) said they had difficulty keeping warm prior to this admission. The majority of patients said they could not manage to keep warm in the winter without financial hardship. In addition, 29% said they had reduced the amount spent on food in order to pay for fuel bills. This study suggests that cold may contribute to hospital admissions in elderly patients. This should have implications for government spending and taxation policy on domestic heating.
Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with Bacillus Calmette-Guérin Failure in Patients with Non–muscle-invasive Bladder Cancer
Authors: Trine Strandgaard, Sia Viborg Lindskrog, Iver Nordentoft, Emil Christensen, Karin Birkenkamp-Demtröder, Tine Ginnerup Andreasen, Philippe Lamy, Asbjørn Kjær, Daniel Ranti, Yuanshuo Alice Wang, Christine Bieber, Frederik Prip, Julie Rasmussen, Torben Steiniche, Nicolai Birkbak, John Sfakianos, Amir Horowitz, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Journal: European Urology (2022)

The functional status of immune cells in the tumor microenvironment and tumor characteristics may explain bacillus Calmette-Guérin (BCG) failure in high-risk non-muscle-invasive bladder cancer (NMIBC).To characterize molecular correlates of post-BCG high-grade (HG) recurrence using multiomics analysis.Patients with BCG-treated NMIBC (n = 156) were included in the study. Metachronous tumors were analyzed using RNA sequencing (n = 170) and whole-exome sequencing (n = 195). Urine samples were analyzed for immuno-oncology-related proteins (n = 190) and tumor-derived DNA (tdDNA; n = 187).The primary endpoint was post-BCG HG recurrence. Cox regression and Wilcoxon rank-sum, t, and Fisher's exact tests were used for analyses.BCG induced activation of the immune system regardless of clinical response; however, immunoinhibitory proteins were observed in the urine of patients with post-BCG HG recurrence (CD70, PD1, CD5). Post-BCG HG recurrence was associated with post-BCG T-cell exhaustion (p = 0.002). Pre-BCG tumors from patients with post-BCG T-cell exhaustion had high expression of genes related to cell division and immune function. A high predicted post-BCG exhaustion score for pre-BCG tumors was associated with worse post-BCG HG recurrence-free survival (HGRFS; p = 0.002). This was validated in independent cohorts. Pre-BCG class 2a and 2b tumors (UROMOL2021 scheme) were associated with worse post-BCG HGRFS (p = 0.015). Post-BCG exhaustion was observed in patients with high pre-BCG neoantigen load (p = 0.017) and MUC4 mutations (p = 0.002). Finally, the absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (p = 0.018). The retrospective design and partial overlap for analyses are study limitations.Post-BCG HG recurrence may be caused by T-cell exhaustion. Tumor subtype and pre-BCG tumor characteristics may identify patients at high risk of post-BCG HG recurrence. Urinary measurements have potential for real-time assessment of treatment response.A dysfunctional immune response to bacillus Calmette-Guérin (BCG) therapy may explain high-grade recurrences of bladder cancer.
Re: Giorgio Gandaglia, Elio Mazzone, Armando Stabile, et al. Prostate-specific Membrane Antigen Radioguided Surgery to Detect Nodal Metastases in Primary Prostate Cancer Patients Undergoing Robot-assisted Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: Results of a Planned Interim Analysis of a Prospective Phase 2 Study. Eur Urol.2022;82:411–18
Authors: Bingzhi Wang, Chao Li, Xiaoping Zheng, Kun Yao, Long Wang
Journal: European Urology (2022)
Mitochondrial alterations in fatty liver diseases
Authors: Bernard Fromenty, Michael Roden
Journal: Journal of Hepatology (2022)

Fatty liver diseases can result from common metabolic diseases, as well as from xenobiotic exposure and excessive alcohol use, all of which have been shown to exert toxic effects on hepatic mitochondrial functionality and dynamics. Invasive or complex methodology limits large-scale investigations of mitochondria in human livers. Nevertheless, abnormal mitochondrial function, such as impaired fatty acid oxidation and oxidative phosphorylation, drives oxidative stress and has been identified as an important feature of human steatohepatitis. On the other hand, hepatic mitochondria can be flexible and adapt to the ambient metabolic condition to prevent triglyceride and lipotoxin accumulation in obesity. Experience from studies on xenobiotics has provided important insights into the regulation of hepatic mitochondria. Increasing awareness of the joint presence of metabolic disease-related (lipotoxic) and alcohol-related liver diseases further highlights the need to better understand their mutual interaction and potentiation in disease progression. Recent clinical studies have assessed the effects of diets or bariatric surgery on hepatic mitochondria, which are also evolving as an interesting therapeutic target in non-alcoholic fatty liver disease. This review summarises the current knowledge on hepatic mitochondria with a focus on fatty liver diseases linked to obesity, type 2 diabetes and xenobiotics.
Does the pursuit of scientific excellence serve or hamper translational medical research: an historical perspective from hematological malignancies
Authors: Chris M. Bunce, Farhat L. Khanim, Mark T. Drayson
Journal: Blood Cancer Journal (2022)

Despite enormous global investment, translational medical research faces considerable challenges and patients, and their doctors are frequently frustrated by the apparent lack of research activity or progress. Understanding the factors that prevent innovative research discoveries from making it to clinical trials is a multifaceted problem. However, one question that must be addressed is whether the nature of current research activity and the factors that influence the conduct of pre-clinical research, permit, or hamper the timely progression of laboratory-based observations to proof of concept (PoC) clinical trials. Inherent in this question is to what extent a deep mechanistic understanding of a potential new therapy is required before commencing PoC studies, and whether patients are better served when mechanistic and clinical studies progress side by side rather than in a more linear fashion. Here we address these questions by revisiting the historical development of hugely impactful and paradigm-changing innovations in the treatment of hematological cancers. First, we compare the history and route to clinical PoC, of two molecularly-targeted therapies that are BCR:ABL inhibitors in chronic myeloid leukaemia and all-trans retinoic acid (ATRA) in acute promyelocytic leukaemia (APL). We then discuss the history of arsenic trioxide as additional APL therapy, and the repurposing of thalidomide as effective multiple myeloma therapy. These stories have surprising elements of commonality that demand debate about the modern-day hard and soft governance of medical research and whether these processes appropriately align the priorities of advancing scientific knowledge and the need of patients.
Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis
Authors: Ning Shao, Xueyang Ma, Ying-Ying Zhang, Donghui Yang, Ming Ma, Gong-Li Tang
Journal: Acta Pharmaceutica Sinica B (2022)

Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH-NADPH-SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.
Acquired fluconazole resistance and genetic clustering in Diutina (Candida) catenulata from clinical samples
Authors: Céline Nourrisson, Maxime Moniot, Rose-Anne Lavergne, Estelle Robert, Virginie Bonnin, Ferry Hagen, Frédéric Grenouillet, Claudia Cafarchia, Geraldine Butler, Sophie Cassaing, Marcela Sabou, Patrice Le Pape, Philippe Poirier, Florent Morio
Journal: Clinical Microbiology and Infection (2022)
Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials
Authors: J.L. Perez-Gracia, N. Penel, E. Calvo, A. Awada, H.T. Arkenau, T. Amaral, V. Grünwald, M.F. Sanmamed, L. Castelo-Branco, G. Bodoky, M.P. Lolkema, M. Di Nicola, P. Casali, R. Giuliani, G. Pentheroudakis
Journal: Annals of Oncology (2022)
Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)—a randomized phase II trial of the AIO pancreatic cancer group
Authors: T. Seufferlein, W. Uhl, M. Kornmann, H. Algül, H. Friess, A. König, M. Ghadimi, E. Gallmeier, D.K. Bartsch, M.P. Lutz, R. Metzger, K. Wille, B. Gerdes, C.C. Schimanski, F. Graupe, V. Kunzmann, I. Klein, M. Geissler, L. Staib, D. Waldschmidt, C. Bruns, U. Wittel, S. Fichtner-Feigl, S. Daum, A. Hinke, L. Blome, A. Tannapfel, A. Kleger, A.W. Berger, A.M.R. Kestler, J.S. Schuhbaur, L. Perkhofer, M. Tempero, A.C. Reinacher-Schick, T.J. Ettrich
Journal: Annals of Oncology (2022)
Apoptosis is induced by transforming growth factor-β1 within 5 hours in regressing liver without significant fragmentation of the DNA
Authors: Franziska Oberhammer, Wilfried Bursch, Roman Tiefenbacher, Gertraud Fröschl, Margit Pavelka, Tonio Purchio, Rolf Schulte-Hermann
Journal: Hepatology (1993)

In previous studies we showed that transforming growth factor-β1 induces apoptosis in hepatocyte cultures and regressing livers, the mature form being more potent than the transforming growth factor-β1 latency-associated protein. In this study we addressed the question of whether apoptosis can be induced within a short time after administration of transforming growth factor-β1. Five hours after a single intravenous injection of 25 μg mature transforming growth factor-β1/kg body weight, apoptosis is augmented ninefold in the regressing rat liver. A second preceding application induces no further augmentation. Transforming growth factor-β1 latency-associated protein shows no effect with either regimen. Morphological evaluation shows that 5 hr after injection of transforming growth factor-β1 nearly all apoptotic bodies are already engulfed by their neighbor cells. After homogenization of the transforming growth factor-β1-treated livers, the condensed apoptotic bodies are not destroyed and remain in the nuclear pellet. No DNA fragmentation into oligosomes could be detected after purification of the DNA from the nuclear pellet and application to conventional gel electrophoresis. Application of in situ nick translation, which allows detection of DNA single and double-strand breaks in individual apoptotic bodies, also revealed no substantial fragmentation of the DNA in apoptotic bodies. These studies show that transforming growth factor-β1 is able to induce apoptosis within a rather short time and also suggest that in vivo digestion of the DNA does not lead to chromatin condensation. (HEPATOLOGY 1993;18:1238-1246).
It's Time for BCG Vaccine
Authors: Sol Roy Rosenthal
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In 1968 more than 42,000 new active cases of tuberculosis were reported in the United States. This is a slight decrease from 1967, but the alarming fact is that many large cities are reporting increases in the number of new cases, generally accounted for in the nonwhite population and the slum and ghetto areas The increased new case rate in these underprivileged areas and groups suggests the need for a reappraisal of present prevention programs and an added emphasis for the active and intensive employment of BCG vaccine, a proven vaccine against tuberculosis. Measures recommended by the US Task Force on Tuberculosis,<sup>1</sup>namely, finding cases of tuberculosis by tuberculin testing and x-ray films and chemotherapy, have been instrumental in lowering the incidence of tuberculosis in many localities, but reports show that these procedures have been less successful in highrisk areas. Isoniazid prophylaxis, which has been recommended
Quantitative &lt;italic&gt;In Vitro&lt;/italic&gt; Assay of Cytotoxic Cellular Immunity
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Quantitative In Vitro Assay of Cytotoxic Cellular Immunity Get access Timothy G. Canty, M.D., Timothy G. Canty, M.D. Immunology Branch, National Cancer Institute,4, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar John R. Wunderlich, M.D. John R. Wunderlich, M.D. Immunology Branch, National Cancer Institute,4, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 45, Issue 4, October 1970, Pages 761–772, https://doi.org/10.1093/jnci/45.4.761 Published: 01 October 1970 Article history Received: 23 April 1970 Accepted: 10 June 1970 Published: 01 October 1970
Dose-Response Studies With Nitrosoheptamethyleneimine and its α-Deuterium-Labeled Derivative in F344 Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1982)

A dose-response study of the carcinogenicity of nitrosoheptamethyleneimine (N-HEP) in inbred F344 male and female rats was performed by administration of the nitrosamine at several concentrations in drinking water to groups of 20 rats. The concentrations differed by a factor of nearly 2.5 and ranged from 1.0 to 100 mg/liter. The duration of treatment was 13, 25, 50, or 100 weeks, after which the animals were allowed to die naturally of tumors induced. In most treated groups the incidence of tumors of the upper gastrointestinal tract approached 100%. However, at the higher doses there was an inverse relationship between total dose and survival time of the rats. Matched treatment of groups of rats with N-HEP labeled with deuterium in the alpha positions resulted in longer survival. The slower action of the deuterium-labeled compound, as measured by a lower rate of death from tumors, suggests that cleavage of a carbon-hydrogen bond at an alpha position is a rate-limiting step in carcinogenesis by N-HEP in rats.
Halsted of Johns Hopkins
Authors: W. Penfield
Journal: JAMA (1969)

Sir William Osler was the Professor of Medicine in the universities of McGill, Pennsylvania, Johns Hopkins, and Oxford in brilliant succession. His library of rare books on the history of medicine, collected in Oxford, came to McGill after his death, and Dr. William Francis, Osler's cousin and literary executor, came with them. Francis completed the catalogues,<i>Bibliotheca Osleriana</i>, and lived out his life, from 1929 onward, in Montreal as curator and librarian of the Osler Library.<sup>1</sup> Among the treasures in his care was a small black book closed with a lock and key of silver. Osler had advised Francis that its contents (he called them the "secret history") should not be disclosed until the 100th anniversary of the Johns Hopkins Hospital in 1989. But Francis, as his literary executor, decided otherwise. He read the book and in 1958 wrote, "Now that everyone mentioned in it is dead," it should
Circadian Relationship of Serum Uric Acid and Nitric Oxide
Authors: Eugene L. Kanabrocki
Journal: JAMA (2000)

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Making the Family History Relevant
Authors: Richard C. Juberg
Journal: JAMA (1972)

Though there are several reasons for including family data in a medical history, such information often turns out to be irrelevant. Still, family information may be made relevant by recording certain minimal data about first-degree relatives; by asking five questions designed to survey the family for occurrence of the same problem, related problems, clearly heritable traits, unusual conditions, and consanguinity; and by contructing a pedigree. The first step applies to every history; the second step to most; the third to only a few.
Adverse reactions following pulsed tunable dye laser treatmentof port wine stains in 701 patients
Authors: D.C. SEUKERAN, P. COLLINS, R.A. SHEEHAN-DARE
Journal: British Journal of Dermatology (1997)

The pulsed tunable dye laser (PTDL) is generally considered to have a very low incidence of adverse effects, allowing it to become the treatment of choice for the majority of port wine stains (PWS). The low incidence of adverse effects has led to difficulties in determining the true incidence and type of adverse effect seen with this laser. We therefore undertook a retrospective study of 701 patients with PWS, who received 3877 full treatments to determine the incidence and type of adverse effects seen following treatment with the PTDL. Blistering and crusting were seen in 5·9% and 0·7% of patients, respectively, but were transient events which usually healed without permanent sequelae. Hyperpigmentation was the most frequently observed adverse effect seen in 9·1% of patients but generally showed gradual resolution over 6–12 months. Hypopigmentation was infrequent, seen in 1.4% of patients. The most significant adverse effects were atrophic and hypertrophic scarring seen in 4·3% and 0·7% of patients, respectively. Our observations show that there is a small but definite risk of atrophic scarring with a predisposition for younger patients. Hypertrophic scarring can occur albeit rarely and there may be a predisposition towards the neck. In most cases test areas were not predictive of scarring. This underlines the need for a full discussion of scarring risk in patients with PWS undergoing treatment with the PTDL.